Bioaffinity methods and principles are being developed which can be used for characterizing functional interaction properties, including multi-molecular assembly, of biological macromolecules and to design polypeptides de novo which recognize protein surfaces. A major study has been designed to evaluate the potential to adapt bioaffinity chromatography to extant high performance liquid chromatography technology. Silica-based matrices are being used to measure protein-protein, peptide-protein, and peptide-peptide interactions, for neuroendocrine peptides and proteins and their precursors as well as well-understood "model" proteins. Analytical high performance affinity chromatography also is being used as an evaluative tool to design and chemically synthesize peptides de novo which can recognize protein surfaces specifically and ultimately be used for protein isolation and for diagnostic characterization of macromolecular recognition properties. Overall analytical high performance affinity chromatographic methods which result from this study provide potentially important analytical biochemistry tools both for characterizing basic properties of macromolecules and for microscale molecular profiling and diagnosis.